- Preparation method of tofacitinib intermediate cis-1-benzyl-N, 4-dimethylpiperidine-3-amine dihydrochloride
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The invention discloses a preparation method of a tofacitinib intermediate cis-1benzyl-N, 4-dimethyl piperidine-3-amine dihydrochloride. The synthetic method comprises the following steps: taking 3-bromo-4-methylpyridine as an initial raw material, performing substitution reaction with amine to obtain a compound III, and performing acetyl or tert-butyloxycarbonyl protection and catalytic hydrogenation on the compound III to obtain a piperidine compound V. The compound V and benzaldehyde are subjected to reductive amination or react with benzyl halide to obtain a compound VI. A protecting groupis removed from the compound VI, and a hydrochloride compound I. 2HCl is formed at the same time. The synthesis method is simple to operate, high in total yield, high in product purity, stable in quality and suitable for industrial production.
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Paragraph 0046; 0060-0062
(2021/01/29)
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- Tropsch process for cloth intermediate (3 R, 4 R) - N, 4 - dimethyl -1 - benzyl -3 - amino piperdine and its oxalate salt hydrate of new synthetic method
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The invention relates to a supporting france for cloth intermediate (3 R, 4 R) - N, 4 - dimethyl - 1 - benzyl - 3 - amino piperdine and its oxalate salt hydrate of new synthetic method. In order to 3 - amino - 4 - methyl pyridine as the starting material, its amino with orthoformate [...] is generated by the reaction, after after simple concentration, for the metal borohydride reduction to obtain N - methyl derivatives; Boc protection after the, re-covering and into a quaternary ammonium salt, the metal borohydride reduction, then the Rh catalyst for selective hydrogenation, form an enriched (3 R, 4 R - rel -) configuration of compounds, hydrochloric acid/alcohol system deprotected and into salt splitting removing (3 R, 4 S - rel -) isomer to, the resulting (3 R, 4 R - rel -) configuration product for free after L - DTTA obtained through splitting 3 R, 4 R - configuration product; splitting the resulting salts are free after through, into the oxalate purification, to further remove the residual small amount of 3 S, 4 S - isomer so as to obtain a corresponding high-purity and high optical purity (3 R, 4 R) - N, 4 - dimethyl - 1 - benzyl - 3 - amino piperdine. The method of the invention more beneficial for safe, simple and convenient of industrialized scale preparation Tropsch process for cloth intermediate (3 R, 4 R) - N, 4 - dimethyl - 1 - benzyl - 3 - amino piperdine oxalic acid salt hydrate.
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Paragraph 0052; 0054
(2019/04/04)
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- Synthesis method for preparing intermediates of tofacitinib
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The invention provides a novel method for synthesizing primary ring cis-4-methyl-3-methylamino-1-benzylpiperidine bis-hydrochloride of tofacitinib. The primary ring cis-4-methyl-3-methylamino-1-benzylpiperidine bis-hydrochloride is made from 3-halogenation-picoline. The novel method includes steps of catalytic Ullman coupling, 3-halogenation-picoline and benzyl halide salifying, hydroboration reagent reduction, salifying and the like to obtain target compounds. The method has the advantages of simple conditions, easily available reagents and operational safety.
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Paragraph 0038-0040; 0049-0050; 0058; 0059; 0063; 0064
(2018/11/04)
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- Novel method for synthesizing cis-1-benzyl-3-methylamino-4-methyl-piperidine
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The invention provides a novel method for synthesizing cis-1-benzyl-3-methylamino-4-methyl-piperidine. The method has the advantages that aminopyridine is used as the raw material, the original two-step arylamine methylation becomes one-step reaction, unfriendly lithium aluminum hydrogen reduction is avoided, toxic controlled product methyl chloroformate is avoided, the used raw materials are simple and easy to obtain, the method is suitable for industrial production, the generation of a large amount of aluminum-containing wastewater is reduced, production cycle is shortened evidently, and productivity is increased.
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Paragraph 0014; 0017; 0018
(2018/10/19)
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- A synthetic cis - 1 - benzyl - 3 - methylamino - 4 - methyl - piperidine
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The invention relates to a method for synthesizing cis-1-benzyl-3-methylamino-4-methyl-piperidine, in particular to a method for synthesizing cis-1-benzyl-3-methylamino-4-methyl-piperidine by taking 1-benzyl-3-methylamino-4-methyl-piperidine bromide as an
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Paragraph 0031; 0033
(2017/08/25)
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- A SYNTHESIS OF 1-METHYL-2-OXO-3H-PYRROLOPYRIDINE
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A short route to 1-methyl-6-azaoxindole is described involving di-lithiation of 4-methyl-3-(methylamino)pyridine and CO2 addition.
- Faita, Giuseppe,Pozzi, Giovanni,Righetti, Pier Paolo,Tacconi, Gianfranco
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p. 437 - 438
(2007/10/02)
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